Pareto optimal flexible alignment of molecules using a non-dominated sorting genetic algorithm

The use of multi-objective function optimization to superimpose a flexible source molecule onto a rigid target molecule is explored. The objective functions are the SEAL similarity score between the source and target molecules, which has to be maximized, and the conformational strain of the source molecule, which has to be minimized. The optimization algorithm used is an elitist non-dominated sorting genetic algorithm. The algorithm is tested with the superposition of two non-nucleoside HIV-reverse transcriptase inhibitors and the superposition of methotrexate onto dihydrofolate.